Anterior cruciate ligament (ACL) reconstruction is the 6th most common orthopaedic procedure. Disruption of the ACL leads to altered knee function and significantly increases the risk for osteoarthritis (OA). Current methods to reconstruct the ACL are generally perceived to be successful; however, several recent meta- analyses have indicated that normal structure and function of the knee is restored only 60% to 70% of the time and 60 to 90% have radiographic evidence of knee OA within 10 to 20 years. Though the causes of post- traumatic OA are almost certainly multifactorial, a significant factor contributing to the increased risk for OA following ACL injury and surgery may be failure to restore normal anatomy and kinematics of the knee. We have previously shown that conventional single-bundle (SB) ACL reconstruction fails to restore normal knee kinematics, leading to altered patterns of joint loading. There is growing support for the theory that cartilage adapts to its local loading environment and abnormal joint loading may play an important role in the development and progression of OA. Our understanding of ACL anatomy has also improved over the last few years, revealing the shortcomings of current surgical techniques to restore anatomy of the ACL. We have developed double-bundle (DB) surgical procedures to restore normal anatomy of the anteromedial (AM) and posterolateral (PL) bundles of the ACL. The underlying principle for this approach is that more anatomical graft placement will lead to better knee mechanics, which are necessary for improved long-term outcome. To determine if anatomic DB ACL reconstruction can effectively restore normal dynamic knee function, we will conduct a double-blind randomized clinical trial to compare SB vs. anatomic DB ACL reconstruction. The specific aims of this study are to determine if DB is better than SB ACL reconstruction in terms of 1) dynamic knee function and 2) clinical outcomes. We will randomly assign 160 subjects with an isolated ACL injury to SB or DB ACL reconstruction and will follow the subjects for 2 years. We will utilize a unique combination of high-speed biplane radiography (for accurate assessment of knee kinematics) and 3D imaging (MRI and CT, to define joint and cartilage morphology) to characterize joint kinematics and cartilage surface interactions during functional tasks. Clinical outcomes will include laxity, range of motion, functional strength and patient-reported symptoms, function and activity. Successful completion of this study will provide evidence of the efficacy of anatomic DB ACL reconstruction for restoring normal knee mechanics and improving clinical outcomes. If the results show a clear benefit of this procedure, then a sound basis will have been established for future studies to assess the benefits of anatomic DB ACL reconstruction on long-term clinical outcomes and joint health. PUBLIC HEALTH RELEVANCE: Current treatments for ACL injury fail to restore normal function of the knee and prevent the development of knee arthritis. The purpose of this study is to evaluate a novel surgical technique designed to restore the normal, double-bundle anatomy of the ACL, to determine if it can better restore normal motion of the knee and lead to improved outcomes in comparison to current methods to reconstruct the ACL. The results of this study may lead to improved recovery after this common injury and lessen the risk for future development of knee arthritis.